There are mechanisms (other than specific immunity) which regulate the neoplastic process in somatic cells. We described and discussed our model, experimental murine leukemia, which allows an analytical experimental approach to these mechanisms. (1) Lymphocytes differentiated to T cells become completely refractory to Friend virus (FV) whereas those differentiated to B cells are permissive to antigenically and functionally altered by FV. However, only activated or antigen sensitized B cells are permissive to oncornaviruses (FV and others). This implies two cellular regulatory mechanisms, one in T cells (absolute resistance) and the other in virgin B cells (relative resistance). (2) Activated T cells release factor(s) which stimulate various bone marrow-derived cell targets for oncornavirus. As stimulation is associated with permissiveness, these factors enhance leukemogenesis and their level in organisms may indicate a disposition to neoplasia. This represents a humoral control of neoplasia. On the basis of this data, the following objectives and experimental plans were set for the proposed project: (a) to analyze the process associated with the conversion of bone-marrow cells to T cells which makes the latter refractory to FV; (b) to determine the nature of the processes which "switch on" permissiveness to oncornaviruses in activated B cells; (c) to determine the conditions required for the enhancing effect of T cell factor(s) on virus-induced and spontaneous leukemias; and (d) to examine the possibility of a clinical application of the phenomenon in the future. These experiments employ in vitro and in vivo studies on lymphocyte differentiation, their infection and transformation (antigenic alteration) with leukemia agents, and various assays to determine the effect of humoral factor(s).